Improvement of obesity and type 2 diabetes in PLD2-targeted mice. (A) Schematic illustration of experiments to investigate the therapeutic effects of CAY10594 in obese mice. (B and C) Body weight curve (B) and daily food intake levels (C) of vehicle- or CAY10594-injected obese WT mice (n = 6/group). (D) Representative images of mice (top), fat depots and liver (bottom) from vehicle- or CAY10594-injected obese mice (n = 6/group). Scale bars, 1 cm. (E) Weights of fat and lean mass from vehicle- or CAY10594-injected obese mice (n = 6/group). (F) Weights of fat depots and liver from vehicle- or CAY10594-injected obese mice (n = 6/group). (G) Representative images of H&E staining of diverse fat depots and liver from vehicle- or CAY10594-injected obese mice. Scale bars, 25 µm. (H) Average EE at day and night from vehicle- or CAY10594-injected obese mice (n = 6/group). (I and J) Blood glucose concentrations during O-GTT (I) and ITT (J) in fasted vehicle- or CAY10594-injected obese mice (n = 6/group). (K–M) Body weight curve (K), representative images (L), and daily food intake levels (M) of HFD-induced control and Pld2 Ad-KO mice for 12 wk (n = 6/group). Scale bars, 1 cm. (N) Representative images of fat depots and liver of HFD-induced control and Pld2 Ad-KO mice for 12 wk (n = 6/group). Scale bars, 1 cm. (O) Weights of fat and lean mass of HFD-induced control and Pld2 Ad-KO mice for 12 wk (n = 6/group). (P) Weights of fat depots and liver from HFD-induced control and Pld2 Ad-KO mice for 12 wk (n = 6/group). (Q and R) Representative images of H&E staining of diverse fat depots (Q) and liver (R) from HFD-induced control and Pld2 Ad-KO mice for 12 wk (n = 6/group). (S and T) Fed and fasted blood concentrations of glucose (S) and insulin (T) from HFD-induced control and Pld2 Ad-KO mice for 12 wk (n = 6/group). (U and V) Blood glucose concentrations during O-GTT (U) and ITT (V) in fasted HFD-induced control and Pld2 Ad-KO mice for 12 wk (n = 6/group). (W) Representative Western blot images of pAktS473, Akt, pGsk3βS9, and Gsk3β in epiWAT and liver from HFD-induced control and Pld2 Ad-KO mice for 12 wk. The data are presented as mean ± SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001 by two-way ANOVA (B, I–K, U, and V) or two-tailed Student’s t test (C, E, F, H, O, P, S, and T). Data are representative of three independent experiments (A–W). Veh, vehicle.